**4. Carotid artery dolichoarteriopathies**

Atherosclerosis is the most frequent cause of extracranial carotidartery disease. [111] However, although atheromatous pathology of the carotid bulb and bifurcation is a major causes of stroke, other causes of carotid disease may also cause vessel occlusion, such as fibrodysplasia, trauma (with subsequent dissection of carotid arteries), aortic arch pathology as in Takayasu disease, and aortic dissection. [112]

Among nonatheromatous alterations of the carotid arteries, interest has long been placed on specific anatomical abnormalities called dolichoarteriopathies.

Carotid dolichoarteriopathies can be classified into three different types [113](Figure 17).Type 1: tortuosity – a nonrectilinear stretch of an artery with an angulation >90; type 2: loop – a 360 angulation of an artery on its transverse axis (''coil'' configuration) (Figure 18); type 3: kinking – the inflection of 2 or more segments of an artery with an internal angle of 90° or less. (Figures 19 and 20).

Dolichoarteriopathies of carotid arteries are frequent, ranging between 10% and 45%. [114] For type 3, a prevalence of 5% to 25% has been described.[115,116]

Published studies have reached disparate conclusions with regard to the origin or cause of carotid dolichoarteriopathies, as well as their hemodynamic and prognostic significance. [114-119] Mukherjee and Inahara [119] proposed that carotid kinking would induce turbulent flow, thus favoring intimal ulceration, platelet deposition, and distal thrombus embolism. Other investigators similarly believe that a causal connection exists between cerebral flow alteration and severe carotid dolichoarteriopathies, to the point of proposing surgical correc‐ tion of kinking and coiling to prevent stroke. [14,120,121]

Conversely,other authors consider carotid dolichoarteriopathies as a mere anatomical variety, devoid of clinical consequences. [122]

Establishing the clinical impact of dolichoarteriopathies is further complicated by the fact that the mechanisms responsible for their formation are still debated.

**Figure 19.** A: Color flow Doppler imaging discloses an internal carotid artery kinking.B: Color and pulsed-wave Dop‐ pler showed turbulences at the site of the kinking. However, both maximum systolic velocity and end-diastolic velocity

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**Figure 20.** A double angled internal carotid artery showing a S shaped configuration (image corresponding to color

of internal carotid arteries were substantially unaffected by kinking

Doppler ultrasound)

**Figure 17.** The different types of dolichoarteriopathies, according to the definition of Weibel and Fields.

**Figure 18.** Color flow Doppler imaging shows circular-shaped internal carotid artery

Conversely,other authors consider carotid dolichoarteriopathies as a mere anatomical variety,

Establishing the clinical impact of dolichoarteriopathies is further complicated by the fact that

**Figure 17.** The different types of dolichoarteriopathies, according to the definition of Weibel and Fields.

**Figure 18.** Color flow Doppler imaging shows circular-shaped internal carotid artery

the mechanisms responsible for their formation are still debated.

devoid of clinical consequences. [122]

54 Carotid Artery Disease - From Bench to Bedside and Beyond

**Figure 19.** A: Color flow Doppler imaging discloses an internal carotid artery kinking.B: Color and pulsed-wave Dop‐ pler showed turbulences at the site of the kinking. However, both maximum systolic velocity and end-diastolic velocity of internal carotid arteries were substantially unaffected by kinking

**Figure 20.** A double angled internal carotid artery showing a S shaped configuration (image corresponding to color Doppler ultrasound)

### **4.1. Origin of carotid dolichoarteriopathies — Congenital or acquired?**

One theory maintains that they are pathological alterations caused by arterial aging and/or changes induced by atherosclerotic remodeling, which would cause the vessel to bend, [114,123-126] while other reports do not support an association between dolichoarteriopathies and cardiovascular risk status. [122,127,128] Alternatively, it has therefore been postulated that they have an embryological origin. Indeed, Kelly [129] observed that carotid arteries may be kinked or show loops at some point during intrauterine development, when the descent toward the mediastinum occurs enabling the union of the third aortic arch with the dorsal aorta.

The possibility that carotid dolichoarteriopathies may have an embryological origin had also been suggested in the past. Again, however, those reports were not conclusive. Sometimes, this was because of the small numbers of cases studied. In this respect, Weibel and Fields [113] described at angiography 14 cases of anatomical abnormalities in patients aged between1 and 20 years, while Sarkari et al [133] reported 8 children (aged 9 months to 16 years) with symptomatic carotid kinkings and coilings. In a substantially largerstudy, there may have been a selection bias [134] in that case, 282 angiographies of neck vessels were obtainedin patients aged between 6 months and 82 years. The authors found that prevalence ofcarotid abnormal‐ ities in adults was 24% and even greater (43%) in children. Although that finding may seemingly support the view that in fact there is no association with aging and that dolichoar‐ teriopathies have an embryological origin, the significance of such a high frequence in children might have been restricted to the peculiar population studied, as it is quite conceivable that children who were subjected to an invasive procedure such as angiography underwent it

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Togay-Isikay et al,through noninvasive Doppler ultrasonography assessment, observed carotid dolichoarteriopathies in 24.6% of a consecutive patient series, with no apparent relation between carotid alterations and cardiovascular risk factors. [122] In 1924,Cairney [135] had already reported autoptic findings in fetuses from the fifth month in whom morphological carotid arteries abnormalitieswere observed. In this respect, it is important to notice that the vascular wall in fetus develops from mesenchymal cells islets; in any artery, the tunica muscularis develops first in the main trunk and later in its branches. The proximal portion of the internal carotid artery originates from the third aortic arch while the more distal parts originate from the left dorsal aorta. [130] Harrison and Dávalos [130] suggested that develop‐ ment of carotid arteries and of skeletal system might be asynchronous, the different velocity explaining the tortuous path.Ochsner et al [136] proposed that fibromuscular dysplasia occurring during fetal life, located in a sector of the carotid artery, would be responsible for subsequent weakening and kinking of the wall at that level. Contrary to this specific hypoth‐ esis, however, is the fact that presence of fibromuscular dysplasia in areas with dolichoarter‐

Regarding the issue of congenital or adquired condition of dolichoarteriopathies, our group conducted an observational study involving 885 participants of either sex, aged between

Patients were divided into 2 groups (G): G1 (control, healthy participants) n = 245. It consisted of infants, children, and adolescents up to 15 years of age (mean 6 + 3 years) from a town of 43 000 inhabitants just outside of Buenos Aires; these children participated in a voluntary screening health program, approved by their parents, under the patronage of the local municipality that was performed in the hospital and different schools. Group 2 (G2; n = 640) consisted of patients from 16 to 90 years of age (mean 57+8 years) in whom diagnostic color Doppler ultrasonography investigation of neck vessels had been requested for clinical suspicion of atherosclerotic disease. Patients were assessed with regard to presence of cardiovascular risk factors (hypertension, dyslipidemia, smoking). Presence of atheromatous

plaques in the regions affected by dolichoarteriopathies was also evaluated.

because of a high clinical suspicion of carotid abnormalities.

iopathies is very rare.[137-139]

newborn(4 hour 30 minutes) to 90 years old. [16]

Obviously, as these 2 etiological theories are so different from each other, they may also entail different implications both clinically and prognostically. Part of the uncertainty derives from the fact that previous observations had been made in small studies or in selected populations. [122-128] Therefore, it would be important to establish which theory has more solid basis.

Prevalence varies according to different diagnostic methodology and patients' inclusion criteria, but in aggregate they concur to indicate that this is a rather frequent finding. In contrast, lack of consensus exists over the clinical and prognostic significance of these altera‐ tions or even about their etiology. Much of the controversy revolves around a ''nature- ornurture'' type of issue, that is, whether carotid dolichoarteriopathies develop late in life as a manifestation of vessel remodeling, particularly in individuals at risk of atherosclerosis, or rather they originate from alterations of embryological development.

With regard to the possibility that dolichoarteriopathies may be the result of a degenerative process, over the years several hypotheses have been put forward trying to explain how they may develop. Some of these seem quite unlikely, such as the possibility that carotid kinking could be due to kyphosis or lordosis of the spine, which might deviate the carotid axis, [130] or that inflammation of the tissues around the carotid arteries would cause them to retract. [131] Other investigators have proposed that arterial hypertension would produce alterations in the wall over time, which would favor its weakening withsubsequent kinking of the artery, [121-123] while other authors hypothesized a relationship between aging and arterial ana‐ tomical abnormalities. [114,126]

Data gathered in modern times also do not help in establishing firm conclusions. Two rather large reports by Ghilardi et al [125] and Del Corso et al [132] described a great prevalence of hypertension and atherosclerosis in patients with carotid dolichoarteriopathies; however, both studies lack a group of normal participants, and deal with a population of patients selected for vascular pathology, and in whom predominance of such cardiovascular risk factors is expected. Pancera et al [127] have reported an association between carotid artery kinking and age and with hypertension as well. However, in that study, prevalence of carotid abnormalities was actually identical across the age groups from 60 to>80 years, which represented 87% of their cohort: younger patients, in whom prevalence was apparently lower, were instead too few to make a solid comparison. This same reasoning applies to the effect of hypertension reported in that study, which was actually based on about a dozen patients. [127]

The possibility that carotid dolichoarteriopathies may have an embryological origin had also been suggested in the past. Again, however, those reports were not conclusive. Sometimes, this was because of the small numbers of cases studied. In this respect, Weibel and Fields [113] described at angiography 14 cases of anatomical abnormalities in patients aged between1 and 20 years, while Sarkari et al [133] reported 8 children (aged 9 months to 16 years) with symptomatic carotid kinkings and coilings. In a substantially largerstudy, there may have been a selection bias [134] in that case, 282 angiographies of neck vessels were obtainedin patients aged between 6 months and 82 years. The authors found that prevalence ofcarotid abnormal‐ ities in adults was 24% and even greater (43%) in children. Although that finding may seemingly support the view that in fact there is no association with aging and that dolichoar‐ teriopathies have an embryological origin, the significance of such a high frequence in children might have been restricted to the peculiar population studied, as it is quite conceivable that children who were subjected to an invasive procedure such as angiography underwent it because of a high clinical suspicion of carotid abnormalities.

**4.1. Origin of carotid dolichoarteriopathies — Congenital or acquired?**

56 Carotid Artery Disease - From Bench to Bedside and Beyond

rather they originate from alterations of embryological development.

tomical abnormalities. [114,126]

aorta.

One theory maintains that they are pathological alterations caused by arterial aging and/or changes induced by atherosclerotic remodeling, which would cause the vessel to bend, [114,123-126] while other reports do not support an association between dolichoarteriopathies and cardiovascular risk status. [122,127,128] Alternatively, it has therefore been postulated that they have an embryological origin. Indeed, Kelly [129] observed that carotid arteries may be kinked or show loops at some point during intrauterine development, when the descent toward the mediastinum occurs enabling the union of the third aortic arch with the dorsal

Obviously, as these 2 etiological theories are so different from each other, they may also entail different implications both clinically and prognostically. Part of the uncertainty derives from the fact that previous observations had been made in small studies or in selected populations. [122-128] Therefore, it would be important to establish which theory has more solid basis.

Prevalence varies according to different diagnostic methodology and patients' inclusion criteria, but in aggregate they concur to indicate that this is a rather frequent finding. In contrast, lack of consensus exists over the clinical and prognostic significance of these altera‐ tions or even about their etiology. Much of the controversy revolves around a ''nature- ornurture'' type of issue, that is, whether carotid dolichoarteriopathies develop late in life as a manifestation of vessel remodeling, particularly in individuals at risk of atherosclerosis, or

With regard to the possibility that dolichoarteriopathies may be the result of a degenerative process, over the years several hypotheses have been put forward trying to explain how they may develop. Some of these seem quite unlikely, such as the possibility that carotid kinking could be due to kyphosis or lordosis of the spine, which might deviate the carotid axis, [130] or that inflammation of the tissues around the carotid arteries would cause them to retract. [131] Other investigators have proposed that arterial hypertension would produce alterations in the wall over time, which would favor its weakening withsubsequent kinking of the artery, [121-123] while other authors hypothesized a relationship between aging and arterial ana‐

Data gathered in modern times also do not help in establishing firm conclusions. Two rather large reports by Ghilardi et al [125] and Del Corso et al [132] described a great prevalence of hypertension and atherosclerosis in patients with carotid dolichoarteriopathies; however, both studies lack a group of normal participants, and deal with a population of patients selected for vascular pathology, and in whom predominance of such cardiovascular risk factors is expected. Pancera et al [127] have reported an association between carotid artery kinking and age and with hypertension as well. However, in that study, prevalence of carotid abnormalities was actually identical across the age groups from 60 to>80 years, which represented 87% of their cohort: younger patients, in whom prevalence was apparently lower, were instead too few to make a solid comparison. This same reasoning applies to the effect of hypertension

reported in that study, which was actually based on about a dozen patients. [127]

Togay-Isikay et al,through noninvasive Doppler ultrasonography assessment, observed carotid dolichoarteriopathies in 24.6% of a consecutive patient series, with no apparent relation between carotid alterations and cardiovascular risk factors. [122] In 1924,Cairney [135] had already reported autoptic findings in fetuses from the fifth month in whom morphological carotid arteries abnormalitieswere observed. In this respect, it is important to notice that the vascular wall in fetus develops from mesenchymal cells islets; in any artery, the tunica muscularis develops first in the main trunk and later in its branches. The proximal portion of the internal carotid artery originates from the third aortic arch while the more distal parts originate from the left dorsal aorta. [130] Harrison and Dávalos [130] suggested that develop‐ ment of carotid arteries and of skeletal system might be asynchronous, the different velocity explaining the tortuous path.Ochsner et al [136] proposed that fibromuscular dysplasia occurring during fetal life, located in a sector of the carotid artery, would be responsible for subsequent weakening and kinking of the wall at that level. Contrary to this specific hypoth‐ esis, however, is the fact that presence of fibromuscular dysplasia in areas with dolichoarter‐ iopathies is very rare.[137-139]

Regarding the issue of congenital or adquired condition of dolichoarteriopathies, our group conducted an observational study involving 885 participants of either sex, aged between newborn(4 hour 30 minutes) to 90 years old. [16]

Patients were divided into 2 groups (G): G1 (control, healthy participants) n = 245. It consisted of infants, children, and adolescents up to 15 years of age (mean 6 + 3 years) from a town of 43 000 inhabitants just outside of Buenos Aires; these children participated in a voluntary screening health program, approved by their parents, under the patronage of the local municipality that was performed in the hospital and different schools. Group 2 (G2; n = 640) consisted of patients from 16 to 90 years of age (mean 57+8 years) in whom diagnostic color Doppler ultrasonography investigation of neck vessels had been requested for clinical suspicion of atherosclerotic disease. Patients were assessed with regard to presence of cardiovascular risk factors (hypertension, dyslipidemia, smoking). Presence of atheromatous plaques in the regions affected by dolichoarteriopathies was also evaluated.

Coiling prevalence was similar in healthy participants (G1 4%; n ¼ 10) and in patients (G2 3%; n = 19; NS;). At the same time, kinking prevalence in G1 was 27% (n = 67), and it was 22% (n = 143) in G2, which did not show any statistically significant association either Atheromatous plaques intrakinking were only observed in 3 G2 patients (0.47%). In this group, 56.2% of patients presented carotid atherosclerotic disease. Within G2 patients, prevalence of cardio‐ vascular risk factors evaluated individually was similar when patients were divided according to presence or absence of kinking and/or coiling.

Grego et al. [156] assured that natural history of carotid dolichoarteriopathies is practically unknown but in some cases surgery would be justified, such as: a) transient ischemic attack (hemispheric symptoms); b) asymptomatic patients with a kinking angle less than 30° together with contralateral carotid occlusion; c) patients with non-hemispheric symptoms after evaluating that there were no other possible neurological or non-neurological causes through positive results of the following studies: 1) Doppler ultrasonography of neck vessels with increase in circulatory velocity; 2) computerized cerebral tomography and MRI angiography of ischemic lesions in the ipsilateral hemisphere and 3) Inversion of the circulatory flow in the anterior cerebral artery and its reduction in the middle cerebral artery, in both cases in relation

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Recent papers regarding surgical intervention on carotid arteries kinking, totalizing roughly 150 patients, flaw to show convincing evidence on the benefits of intervention.[158-160]

Up to now, there are no guidelines nor is there consensus (with a level of recommendation)

Taking into account the pitfalls in measuring stenotic percentage in bended arteries, it is our point of view that manuscripts reporting big number of operated patients with carotid dolichoareriopathies failed in the diagnostic ultrasonographic criterions of stenotic kinkings and coils, furthermore, there is no mention about which method for angiographic measures were used. Also, most of their patients had cardiovascular risk factor which could have been the responsible of the neurological symptoms remaining doubts about their true relation with

Our group conducted an investigation study regarding the clinical implications in the genesis of neurological complications related to kinking and looping (coiling) of the carotid arteries. [162] Sixty patients with non-atheromatous carotid kinkings were subjected to head rotation tests, and were studied by carotid artery B-mode, color Doppler ultrasonography, and scanning the ophthalmic artery in order to assess the hemodynamic behavior of carotid dolichoarteriopathies. Results suggested that carotid dolichoarteriopathies are not the cause of neurological events or symptoms taking into account that no events were recorded during the study, and registering significant reduction in the velocities in the ophthalmic artery in only 3 of the 60 cases studied, in performing the head rotation tests.in the patient cohort. 23 % (n=14) were asymptomatic as only 6 patients were referred for stroke or transient ischemic attack. Consecuently we concluded that carotid dysembryoplasias, would not cause neuro‐

Computerized tomography angiography (CTA) and magnetic resonance angiography (MRA) showed excellent ability to depict the malformation of cervical segment of internal carotid artery and its relationship with surrounding structures, which could protect carotid artery

It may be concluded that dolichoartheriopathies recognize a congenital origin other than an acquired condition, based on controlled studies regarding juvenile control cases. Additionally, in the current state of knowledge, it unlikely appears that these dolichoartheriorpathies induce

to the rotation and flexo-extension maneuvers of the head.

for surgical treatment of dolichoarteriopathies.

carotid abnormalities. [157,161]

logical events nor symptoms.

from unintended damage. [163]

relevant symptomatic cerebral ischemia

We observed that the dolichoarteriopathies, namely, kinking and coiling of carotid arteries, had similar frequency across all ages, from newborn infants to elderly individuals. Further‐ more, their prevalence was unrelated to the presence of cardiovascular risk factors or of frank atherosclerotic pathology of carotid artery. Collectively, these findings suggest that carotid dolichoarteriopathies are a result of alterations in embryological development rather than of vascular remodeling secondary to aging and/or atherosclerosis. [16]
